Stem cells are pluripotent cells with remarkable potential to develop into many different cell types in the body during early life and growth. Stem cells hold promise for regenerative medicine and cell therapy, especially in fields where more personalized medicine approaches are becoming increasingly predominant. For example, a wide variety of progenitor/stem cell therapies are recognized as a promising strategy to repair damaged tissue, such as an ischemic damaged heart. In many tissues, stem cells essentially function as an internal repair system for living animals, dividing essentially without limit to replenish other cells. There are two types of stem cells: embryonic stem cells and non-embryonic “somatic” or “adult” stem cells. Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to pluripotent stem cells.
Although embryonic stem cells are attractive sources for cardiac regeneration due to their high capacity for unlimited proliferation and multipotency, there are several critical issues that need to be overcome for clinical application, including ethical concern and immunological rejection after transplantation. More recently, iPSCs have emerged as a promising cell source to differentiate into functional cardiomyocytes, which can be utilized to regenerate cardiac tissues. The iPSCs possess similar potential as embryonic stem cells in regards to their pluripotency, morphology, proliferative ability, surface antigens, gene expression, and epigenetic status of pluripotent stem cell-specific genes. Additionally, because iPSCs can be easily generated from patients own cells and have the similar potential as embryonic stem cells, generation of iPSC-derived cardiomyocytes is regarded as a promising strategy for treatment of ischemic heart without ethical and immunological issues.
Although stem cells carry promise, there are still challenges for using stem cells, particularly iPCSs for regenerative medicine and cell therapy. Although iPSCs can differentiate into functional cardiomyocytes through embryoid body (EB) differentiation in the presence of specific differentiation signals, the differentiation and reprogramming strategies are not standardized and are most often based on the addition of key growth factors at critical stages of development, making protocols expensive, poorly reproducible, and limited in terms of scale-up. Furthermore, low efficiency and low degree of maturation of cardiomyocytes that are differentiated from iPSCs still limit iPCSs potential for cardiac regeneration application, and no solid method has been established for enhancing iPSCs to differentiate into cardiomyocytes efficiently. Additionally, current differentiation or reprogramming protocols are too slow, and with some protocols currently taking more than a month to develop cardiomyocytes.
There is thus a need in the art to provide novel methods for the accelerated generation of cardiomyocytes from iPSCs.